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Deutsches Arzteblatt International Dec 2019Hypertriglyceridemia affects 15-20% of the adult population and is associated with overweight, metabolic syndrome, and diabetes mellitus. It is often discovered... (Review)
Review
BACKGROUND
Hypertriglyceridemia affects 15-20% of the adult population and is associated with overweight, metabolic syndrome, and diabetes mellitus. It is often discovered incidentally.
METHODS
This review is based on pertinent publications retrieved by a selective literature search, including current guidelines on hypertriglyceridemia.
RESULTS
Elevated triglyceride (TG) levels are causally linked to cardiovascular disease; TG levels above 1000 mg/dL (11.4 mmol/L) can induce acute pancreatitis. The individual risk of cardiovascular disease and of pancreatitis must be estimated in order to decide whether, and how, hypertriglyceridemia should be treated. Lifestyle modifications (cessation of alcohol consumption, reduced intake of rapidly metabolized carbohydrates), weight loss, and blood sugar control are the most effective ways to lower TG levels. The need to lower the low-density lipoprotein (LDL) concentration must be determined on the basis of the cardiovascular risk, independently of the success of the lifestyle changes. Few patients need specific drug treatment to lower the TG level. Fibrates can lower TG concentrations, but their efficacy in combination with statins has not been clearly shown in endpoint studies. A daily dose of 2-4 g omega-3 fatty acids can also lower TG levels. To date, only a single large-scale randomized, blinded trial has shown the efficacy of 4 g of eicosapentaenoic acid ethyl ester per day in lowering the risk in high-risk patients (number needed to treat = 21). Patients with the very rare purely genetic types of hypertriglyceridemia (familial chylomicronemia syndrome) should be treated in specialized outpatient clinics.
CONCLUSION
Hypertriglyceridemia is causally linked to cardiovascular disease and pancreatitis. Lifestyle modifications play a paramount role in its treatment.
Topics: Cardiovascular Diseases; Humans; Hypertriglyceridemia; Pancreatitis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Reduction Behavior
PubMed: 31888796
DOI: 10.3238/arztebl.2019.0825 -
Frontiers in Endocrinology 2020Elevations in plasma triglyceride are the result of overproduction and impaired clearance of triglyceride-rich lipoproteins-very low-density lipoproteins (VLDL) and... (Review)
Review
Elevations in plasma triglyceride are the result of overproduction and impaired clearance of triglyceride-rich lipoproteins-very low-density lipoproteins (VLDL) and chylomicrons. Hypertriglyceridemia is characterized by an accumulation in the circulation of large VLDL-VLDL-and its lipolytic products, and throughout the VLDL-LDL delipidation cascade perturbations occur that give rise to increased concentrations of remnant lipoproteins and small, dense low-density lipoprotein (LDL). The elevated risk of atherosclerotic cardiovascular disease in hypertriglyceridemia is believed to result from the exposure of the artery wall to these aberrant lipoprotein species. Key regulators of the metabolism of triglyceride-rich lipoproteins have been identified and a number of these are targets for pharmacological intervention. However, a clear picture is yet to emerge as to how to relate triglyceride lowering to reduced risk of atherosclerosis.
Topics: Cardiovascular Diseases; Humans; Hypertriglyceridemia; Triglycerides
PubMed: 32477261
DOI: 10.3389/fendo.2020.00252 -
Frontiers in Endocrinology 2020Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for... (Review)
Review
Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.
Topics: Disease Management; Genetic Predisposition to Disease; Humans; Hypertriglyceridemia; Triglycerides
PubMed: 32982991
DOI: 10.3389/fendo.2020.00616 -
BioMed Research International 2018Hypertriglyceridemia is an uncommon but a well-established etiology of acute pancreatitis leading to significant morbidity and mortality. The risk and severity of acute... (Review)
Review
Hypertriglyceridemia is an uncommon but a well-established etiology of acute pancreatitis leading to significant morbidity and mortality. The risk and severity of acute pancreatitis increase with increasing levels of serum triglycerides. It is crucial to identify hypertriglyceridemia as the cause of pancreatitis and initiate appropriate treatment plan. Initial supportive treatment is similar to management of other causes of acute pancreatitis with additional specific therapies tailored to lower serum triglycerides levels. This includes plasmapheresis, insulin, heparin infusion, and hemofiltration. After the acute episode, diet and lifestyle modifications along with hypolipidemic drugs should be initiated to prevent further episodes. Currently, there is paucity of studies directly comparing different modalities. This article provides a comprehensive review of management of hypertriglyceridemia induced acute pancreatitis. We conclude by summarizing our treatment approach to manage hypertriglyceridemia induced acute pancreatitis.
Topics: Acute Disease; Humans; Hypertriglyceridemia; Pancreatitis; Retrospective Studies; Triglycerides
PubMed: 30148167
DOI: 10.1155/2018/4721357 -
Discovery Medicine Feb 2019Acute pancreatitis (AP) is a common and destructive inflammatory condition of the pancreas. Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the... (Review)
Review
Acute pancreatitis (AP) is a common and destructive inflammatory condition of the pancreas. Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the second major cause of AP. Although the association between HTG and AP is well established, HTG as a risk factor of AP in the general population is not well identified. In this review, we summarize recent progress in our understanding of the pathogenesis of HTG-AP and clinical management of this disease. The mechanism responsible for HTG-AP is related to high-level free fatty acid (FFA), microcirculatory disorder, oxidative stress, Ca2+ overload, and genetic polymorphism. Heparin and insulin therapy in diabetic patients with HTG can dramatically reduce triglyceride levels. Use of plasmapheresis is still experimental and better-designed studies are needed to evaluate the promise in the management of HTG-AP. Dietary intervention, lifestyle changes, and control of secondary causes are critical to the management and treatment of HTG-AP.
Topics: Acute Disease; Heparin; Humans; Hypertriglyceridemia; Insulin; Pancreatitis
PubMed: 30939294
DOI: No ID Found -
European Heart Journal Jan 2020Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as... (Review)
Review
Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as important contributors to ASCVD while severe hypertriglyceridaemia raises risk of pancreatitis. While low-density lipoprotein is the primary treatment target for lipid lowering therapy, secondary targets that reflect the contribution of TRL such as apoB and non-HDL-C are recommended in the current guidelines. Reduction of severely elevated triglycerides is important to avert or reduce the risk of pancreatitis. Here we discuss interventions for hypertriglyceridaemia, including diet and lifestyle, established treatments such as fibrates and omega-3 fatty acid preparations and emerging therapies, including various biological agents.
Topics: Humans; Hypertriglyceridemia; Life Style; Triglycerides
PubMed: 31764986
DOI: 10.1093/eurheartj/ehz785 -
Endocrine Reviews Apr 2019Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is a well-established mediator... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is a well-established mediator of atherosclerosis and a key target for intervention for the primary and secondary prevention of ASCVD. However, despite substantial reduction in LDL-C, patients continue to have recurrent ASCVD events. Hypertriglyceridemia may be an important contributor of this residual risk. Observational and genetic epidemiological data strongly support a causal role of triglycerides (TGs) and the cholesterol content within triglyceride-rich lipoproteins (TGRLs) and/or remnant cholesterol (RC) in the development of ASCVD. TGRLs are composed of hepatically derived very low-density lipoprotein and intestinally derived chylomicrons. RC is the cholesterol content of all TGRLs and plasma TGs serve as a surrogate measure of TGRLs and RC. Although lifestyle modification remains the cornerstone for management of hypertriglyceridemia, many novel drugs are in development and have shown impressive efficacy in lowering TG levels. Several ongoing, randomized controlled trials are underway to examine the impact of these novel agents on ASCVD outcomes. In this comprehensive review, we provide an overview of the biology, epidemiology, and genetics of TGs and ASCVD; we discuss current and novel TG-lowering therapies under development.
Topics: Atherosclerosis; Cholesterol; Dyslipidemias; Humans; Hypertriglyceridemia; Lipoproteins; Triglycerides
PubMed: 30312399
DOI: 10.1210/er.2018-00184 -
Current Atherosclerosis Reports Sep 2021Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in... (Review)
Review
PURPOSE OF REVIEW
Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well.
RECENT FINDINGS
NHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP). Residual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.
Topics: Acute Disease; Adult; Angiopoietin-Like Protein 3; Angiopoietin-like Proteins; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypertriglyceridemia; Nutrition Surveys; Pancreatitis; Triglycerides
PubMed: 34515873
DOI: 10.1007/s11883-021-00962-z -
Frontiers in Endocrinology 2020The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When... (Review)
Review
The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situation is termed the multifactorial chylomicronemia syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk.
Topics: Humans; Hyperlipoproteinemia Type I; Hypertriglyceridemia; Pancreatitis
PubMed: 33193106
DOI: 10.3389/fendo.2020.593931 -
The Journal of Clinical Endocrinology... Sep 2012The aim was to develop clinical practice guidelines on hypertriglyceridemia. (Review)
Review
OBJECTIVE
The aim was to develop clinical practice guidelines on hypertriglyceridemia.
PARTICIPANTS
The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration.
CONSENSUS PROCESS
Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.
CONCLUSIONS
The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150-999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of > 1000 mg/dl) be considered a risk for pancreatitis. The Task Force also recommends that patients with hypertriglyceridemia be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease. The Task Force recommends that the treatment goal in patients with moderate hypertriglyceridemia be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate should be used as a first-line agent.
Topics: Evidence-Based Medicine; Exercise Therapy; Humans; Hypertriglyceridemia; Terminology as Topic; Triglycerides
PubMed: 22962670
DOI: 10.1210/jc.2011-3213